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The increasing environmental impact of fish waste has attracted more attention towards developing simple, greener, and effective valorization methods. This study employed optimized milder extraction methods as a potential process intensification strategy to valorize marine and freshwater fish wastes with significant proximate compositions (p < 0.05). Using response surface methodology, the optimized parameters, including lower temperature (60℃), less enzyme concentration (1%), and 1:1 ratio of less toxic solvents, had high desirability levels (˃ 0.92). Although identical chemical functional groups were observed in the infrared spectra, the marine fish waste produced higher oil yields. The physicochemical characteristics of the oils were within the international CXS 329-2017 standard. Palmitic acid (21.21–26.63%), oleic acid (19.78–27.11%), eicosapentaenoic acid (6.02–9.97%), and docosahexaenoic acid (17.00- 20.83%) were the dominant saturated and unsaturated fatty acids in the crude fish oil. The average nutritional quality values of the fatty acids were: polyunsaturated/saturated (0.85–1.33), omega-6/omega-3 (0.18–0.22), atherogenic index (0.35–0.46), thrombogenic index (0.23–0.33), hypocholesterolemic/hypercholesterolemic ratio (2.21–2.77), nutritive value index (0.87–1.68), health-promoting index (2.19–2.82), and fish lipid quality (24.18–28.88). The present research revealed the potentiality of fish waste valorization by optimized milder extraction methods as a possible sustainable approach for targeting the era of zero waste while producing quality crude fish oil. [ABSTRACT FROM AUTHOR]